The improvement effect of astaxanthin on rats with polycystic ovary syndrome by regulating Klotho expression and Wnt/β-Catenin signaling pathway

doi:10.11958/20221727

Abstract

Abstract:

Objective To study the improvement mechanism of astaxanthin in rats with polycystic ovary syndrome (PCOS) by regulating Klotho expression and Wnt/β-Catenin signaling pathway. Methods Thirty PCOS model rats were constructed by intragastric administration of letrozole, and rats were randomly grouped into 6 groups: the model group, the low-dose astaxanthin group (50 mg/kg), the middle-dose astaxanthin groupm (100 mg/kg), the high-dose astaxanthin group (200 mg/kg), the high-dose astaxanthin+no-load group and the high-dose astaxanthin+Klotho knockdown group, with 5 rats in each group. Another 5 SD rats were taken as the control group. After treatment, the body weight and ovarian weight of rats in each group were measured. Forty-five SD rats were modeled in the same way and randomly grouped into: the model group, the astaxanthin group (200 mg/kg), the astaxanthin+Klotho knockdown group, the astaxanthin+lithium chloride group and the astaxanthin+PD98059 (MEK inhibitor) group, with 9 rats in each group. Another 9 SD rats were taken as the control group. After treatment, data of body weight, ovarian weight and volume, the number of cystic follicles in ovarian tissue, levels of serum hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and levels of inflammatory factors prostaglandin 2 (PGE2), interleukin (IL)-17, tumor necrosis factor-α (TNF-α), and IL-18, the expression of Klotho protein and the expression of Wnt/β-Catenin and MEK/ERK signal-related proteins in ovarian tissue were detected in rats of each group. Results Compared with the control group, body weight and ovarian weight were obviously increased in the model group (P<0.05). Compared with the model group, body weight and ovarian weight were all decreased in the low-dose astaxanthin group, the middle-dose astaxanthin group and the high-dose astaxanthin group in a dose-dependent manner (P<0.05). Compared with the high-dose astaxanthin group, body mass and ovarian mass of rats were increased in the high-dose astaxanthin+Klotho knockdown group (P<0.05). There was no significant change in each index of rats in the high dose of astaxanthin+empty load group (P>0.05). Compared with the control group, serum level of FSH, and expression levels of Klotho, p-MEK, p-ERK1/2 proteins in ovarian tissue were obviously decreased in the model group (P<0.05). Body weight, ovarian mass and volume, number of cystic follicles, serum levels of LH, T, PGE2, IL-17, TNF-α and IL-18, and expression levels of Wnt1 and β-Catenin proteins in ovarian tissue were obviously increased in the model group (P<0.05). Compared with the model group, the level of FSH, the expression levels of Klotho, p-MEK and p-ERK1/2 proteins in ovarian tissue were increased in the astaxanthin group (P<0.05). Body weight, ovarian mass and volume, number of cystic follicles, serum levels of LH, T, PGE2, IL-17, TNF-α and IL-18, and expression of Wnt1 and β-Catenin proteins in ovarian tissue were decreased in the astaxanthin group (P<0.05). Knockdown of Klotho, lithium chloride and PD98059 can weaken the improvement effect of astaxanthin on PCOS rats. Conclusion Astaxanthin can down-regulate Wnt/β-Catenin signaling and activate MEK/ERK signaling by up-regulating Klotho, thereby preventing inflammation, improving hormone levels in PCOS rats, reducing number of cystic follicles, and ultimately alleviating the symptoms of polycystic ovaries.

Key words: polycystic ovary syndrome, Wnt signaling pathway, MAP kinase signaling system, Astaxanthin

CLC Number:

R711.75

Figures/Tables 7

References 20

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组别	体质量/g	卵巢质量/mg
对照组	248.94±7.95	614.80±18.62
模型组	339.65±14.52^a	783.14±32.37^a
虾青素低剂量组	311.12±12.30^b	723.26±21.30^b
虾青素中剂量组	282.83±13.81^bc	670.11±22.51^bc
虾青素高剂量组	254.68±11.23^bcd	621.24±14.36^bcd
虾青素高剂量+空载组	251.30±15.01^bcd	623.38±15.01^bcd
虾青素高剂量+Klotho敲低组	332.57±14.94^e	778.19±18.20^e
F	45.050^＊＊	61.260^＊＊

组别	体质量/g	卵巢质量/mg
对照组	248.94±7.95	614.80±18.62
模型组	339.65±14.52^a	783.14±32.37^a
虾青素低剂量组	311.12±12.30^b	723.26±21.30^b
虾青素中剂量组	282.83±13.81^bc	670.11±22.51^bc
虾青素高剂量组	254.68±11.23^bcd	621.24±14.36^bcd
虾青素高剂量+空载组	251.30±15.01^bcd	623.38±15.01^bcd
虾青素高剂量+Klotho敲低组	332.57±14.94^e	778.19±18.20^e
F	45.050^＊＊	61.260^＊＊

组别	体质量/g	卵巢质量/mg	卵巢体积/mm³
对照组	251.78±16.89	612.95±19.03	12.09±0.61
模型组	342.54±35.21^a	789.42±33.12^a	15.87±2.10^a
虾青素组	262.13±20.35^b	620.21±20.38^b	12.63±0.78^b
虾青素+Klotho敲低组	329.84±30.19^c	770.48±29.54^c	15.41±1.81^c
虾青素+氯化锂组	332.16±27.21^c	775.23±30.33^c	15.28±1.59^c
虾青素+PD98059组	326.98±29.44^c	779.10±31.26^c	15.30±1.73^c
F	19.086^＊＊	81.866^＊＊	10.070^＊＊

组别	体质量/g	卵巢质量/mg	卵巢体积/mm³
对照组	251.78±16.89	612.95±19.03	12.09±0.61
模型组	342.54±35.21^a	789.42±33.12^a	15.87±2.10^a
虾青素组	262.13±20.35^b	620.21±20.38^b	12.63±0.78^b
虾青素+Klotho敲低组	329.84±30.19^c	770.48±29.54^c	15.41±1.81^c
虾青素+氯化锂组	332.16±27.21^c	775.23±30.33^c	15.28±1.59^c
虾青素+PD98059组	326.98±29.44^c	779.10±31.26^c	15.30±1.73^c
F	19.086^＊＊	81.866^＊＊	10.070^＊＊

组别	FSH/（IU/L）	LH/（IU/L）	T/（μg/L）	囊状卵泡数量/（个/视野）
对照组	7.74±0.90	4.18±0.51	1.76±0.25	0.69±0.23
模型组	2.65±0.42^a	14.52±1.42^a	5.39±0.63^a	17.72±4.15^a
虾青素组	7.20±0.85^b	4.64±0.73^b	2.08±0.36^b	1.21±0.40^b
虾青素+Klotho敲低组	2.89±0.37^c	14.14±1.22^c	5.07±0.52^c	16.87±4.22^c
虾青素+氯化锂组	2.96±0.45^c	14.27±1.18^c	5.14±0.70^c	17.04±5.40^c
虾青素+PD98059组	3.03±0.39^c	14.01±1.34^c	4.99±0.78^c	16.53±6.32^c
F	138.843^＊＊	186.048^＊＊	77.394^＊＊	35.819^＊＊